Editor's Note: VGF is increased after injury and under conditions of chronic pain and inflammation. Because VGF is found abundantly in the limbic system, it plays a role in regulating metabolism, energy homeostasis, and appetite. The term "cryptogenic" means the cause is unknown.

Prolonged exposure to stress elicits profound effects on homeostasis that may lead to cryptogenic disorders such as chronic fatigue syndrome.

To investigate the pathophysiology associated with the syndrome, we used a rat continuous stress (CS) model where the pituitary represents one of the most affected organs. Here we found that mRNA for VGF (non-acronymic), a member of the granin family, was induced specifically in the intermediate lobe (IL).

This was matched by a concomitant increase at the peptide/protein level assessed by C-terminal antibody. Furthermore, the upregulation of VGF was confirmed by immunohistochemistry in a subset of melanotrophs.

VGF expression was altered in the IL of rats receiving the dopamine D2 receptor agonist bromocriptine or the antagonist sulpiride. In vitro, dopamine dose-dependently decreased the mRNA levels in cultured melanotrophs.

These findings suggest that VGF expression under CS is negatively regulated by dopaminergic neurons projecting from the hypothalamus.